Lycopene and Apo-12′-Lycopenal Reduce Cell Proliferation and Alter Cell Cycle Progression in Human Prostate Cancer Cells

Abstract

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8′-lycopenal, or apo-12′-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12′-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12′-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.

ACKNOWLEDGMENTS

All work was completed at the University of Illinois, Urbana-Champaign. We thank BASF, and especially Hansgeorg Ernst, for providing apo-8′-lycopenal and apo-12′-lycopenal and DSM for providing the lycopene and placebo water-soluble beadlets. We would also like to thank Dr. Alan Lau at the University of Hawaii for providing the Cx43+/+ and Cx43−/− MEF cell lines. This work was supported in part by the American Institute for Cancer Research grant #05A021. BLL was supported by a Jonathan Baldwin Turner Fellowship from the College of Agricultural, Consumer, and Environmental Sciences at the University of Illinois. KZ was supported by a USDA National Needs Fellowship #2005-03750.